MAP4K4mitogen-activated protein kinase kinase kinase kinase 4
Autism Reports / Total Reports
2 / 2Rare Variants / Common Variants
4 / 0Aliases
-Associated Syndromes
-Chromosome Band
2q11.2Associated Disorders
-Relevance to Autism
Rare and potentially damaging missense variants in the MAP4K4 gene were identified in an ASD proband from the MSSNG cohort and an ASD proband from the SPARK cohort (Zhou et al., 2022). Cesana et al., 2022 described two unrelated individuals with de novo loss-of-function variants in the MAP4K4 gene who presented with autism spectrum disorder, developmental delay, tall stature, and minor facial dysmorphic features.
Molecular Function
The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway.
External Links
SFARI Genomic Platforms
Reports related to MAP4K4 (2 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | - | Zhou X et al. (2022) | Yes | - |
2 | Recent Recommendation | - | Cesana M et al. (2022) | Yes | - |
Rare Variants (4)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.3518C>A | p.Thr1173Lys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.57+1del | - | splice_site_variant | De novo | - | Simplex | 36469137 | Cesana M et al. (2022) | |
c.454C>T | p.Arg152Trp | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.1570_1571del | p.Leu524ThrfsTer3 | frameshift_variant | De novo | - | Simplex | 36469137 | Cesana M et al. (2022) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate


Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
1/1/2023

Increased from to 2
Krishnan Probability Score
Score 0.57726955233206
Ranking 630/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99999897904709
Ranking 301/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.94402928353113
Ranking 15916/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score -0.042728784475871
Ranking 10143/20870 scored genes
[Show Scoring Methodology]